Mechanisms underlying renoprotection during renin-angiotensin system blockade

Potential determinants of chronic renal disease (CRD) progression were stud ied in male Munich-Wistar rats subjected to 5/6 nephrectomy and treated wit h candesartan (Csn; n = 30) or enalapril (Ena; n = 27) from 5 wk postsurger y. Despite control of systolic blood pressure (SBP; 24 wk: Csn = 143 +/- 9; Ena = 148 +/- 8 mmHg), urinary protein excretion rates (U-pr V) increased over 24 wk (Csn = 92 +/- 10; Ena = 99 +/- 8mg/day). Glomerulosclerosis scor es (GS) at 24 wk were similar for Csn (42 +/- 7%) vs. Ena (42 +/- 4%), valu es close to those of untreated controls at 12 wk (43 +/- 4%). At 24 wk, SBP and Upr V correlated strongly with GS, together accounting for 72% of the variance in GS. Renal cortex mRNA levels (determined by competitive RT-PCR) for transforming growth factor (TGF)-beta1 and monocyte chemoattractant pr otein (MCP)-1 were elevated in Csn and Ena at 12 wk and remained higher at 24 wk vs. sham. Strong correlations were evident among TGF-beta1, MCP-1, an d interleukin-1 beta and renal injury at 24 wk. Cns and Ena are thus equall y effective renoprotective agents in this model. During renin-angiotensin s ystem inhibition, renoprotection is dependent on control of both SBP and U- pr V. Incomplete suppression of renal cytokine gene expression may also con tribute to CRD progression.